Influence of Genetic Polymorphisms on Clinical Outcomes of Glatiramer Acetate in Multiple Sclerosis Patients

Zarzuelo, María José; Pérez-Ramírez, Cristina; Cura, Yasmín; Carrasco-Campos, María Isabel; Marangoni-Iglecias, Luciana María; Ramírez-Tortosa, María Carmen; Jiménez-Morales, Alberto

doi:10.3390/jpm11101032

Cited by 8 publications

(8 citation statements)

References 104 publications

(140 reference statements)

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“…Among first-line pharmacotherapies in MS is glatiramer acetate; however, the response rate is not greater than 55% due to variability in genetic polymorphisms [72]. Recent studies have demonstrated that long-term disability outcomes tend to be better in MS patients who are treated early with "high-efficacy" medicines including the anti-CD20 monoclonal antibodies rituximab (Rituxan) and ocrelizumab (Ocrevus) targeting B cells, the anti-α4β1 integrin monoclonal natalizumab (Tysabri), the type II topoisomerase inhibitor mitoxantrone (Novantrone), the sphingosine-1-phosphate receptor modulator fingolimod (Gilenya) [73], the monoclonal anti-CD52 alemtuzumab (Campath, Lemtrada) targeting mature lymphocytes, and the purine analogue cladribine (Mavenclad) that delivers "intensive" immune intervention, as compared to patients who are treated with "moderate-efficacy" medications for one or more years prior to "escalation" to the high-potency agents [74,75].…”

Section: Therapeutic Challenges and Biomarker Research In Msmentioning

confidence: 99%

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

et al. 2022

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Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.

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Section: Therapeutic Challenges and Biomarker Research In Msmentioning

confidence: 99%

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

et al. 2022

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“…A combination of agents that modify the course of the disease and have various effects on immunity is used for treatment at different phases of the disease. 4,5 Vitamin plus interferon therapy and the use of medical cannabis have also been studied as methods of treatment in MS. 6,7 This disease leads to a widespread demyelination caused by selective involvement of oligodendrocytes and axonal loss. Additional psychobehavioral symptoms such as anxiety, dementia and depression are also observed.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of different intensity of aquatic exercise in enhancing remyelination and neuronal plasticity using cuprizone model in male Wistar rats

Begum¹,

Subramanian²,

Raghunath³

et al. 2022

Adv Clin Exp Med

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Background. Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). Most exercise studies concentrate on the impact of exercise on cardiovascular system; this study aims to present the effects of exercise of varying intensity on the nervous system. Most recently in MS, positive outcomes were obtained with resistance and high-intensity exercises. This study also analyzes the effects of a prior conditioning program before the induction of demyelination and subsequent neuroprotective effects of such program. Objectives.To study and determine the neuroprotective and remyelinating effects of different intensity of aquatic exercise and a preconditioning exercise program on demyelination induced by oral administration of cuprizone (Cup). Materials and methods.Six groups of animals, each containing 6 rats, were used in the study. The groups were as follows: group I -control group; group II -Cup group; group III -treated with methylprednisolone (MP); group IV -treated with low-intensity exercise (LIE), free swimming for 40 min and high-intensity exercise (HIE); group V -treated with a resistance of 9% body weight and free swimming for 40 min; group VI -treated with preconditioning exercise (free swimming for 40 min for 3 weeks) before Cup administration followed by the same exercise protocol as for group V. All data were analyzed using one-way analysis of variance (ANOVA) with Tukey's test, by means of SigmaPlot v. 14.5 software. Results.Similarly to the MP group, group VI showed a positive outcome. A value of p < 0.001 was considered statistically significant. Also, group VI showed improved areas of remyelination in histopathology, an increased expression of myelin basic protein (MBP), reduced expression of glial fibrillary acidic protein (GFAP) in corpus callosum, and improved gene expression of brain-derived neurotrophic factor (BDNF) in the hippocampus region.Conclusions. General fitness achieved through a preconditioning program combined with HIE showed neuroprotective effects, as evidenced by increased areas of remyelination and improved neuronal plasticity, observed mostly in group VI (conditioning+HIE).

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Section: Introductionmentioning

confidence: 99%

“…In addition, glatiramer acetate, in spite of the fact that it represents an important first-line treatment for MS patients, shows a high variability in responses among patients, with a response rate of nearly 30–55% [ 35 ]. Of note, it has been shown that genetic factors, including polymorphisms in the genes implicated in MS pathogenesis, could influence this variability in the drugs’ effectiveness [ 35 ]. In particular, it has been suggested that there is a relationship between the effectiveness of glatiramer acetate treatment and the presence of polymorphisms in these genes: CD86 , CLEC16A , CTSS , EOMES , MBP , FAS , TRBC1 , IL1R1 , IL12RB2 , IL22RA2 , PTPRT , PVT1 , ALOX5AP , MAGI2 , ZAK , RFPL3 , UVRAG , SLC1A4 , and HLA-DRB1*1501 [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Cytotoxic T-Lymphocyte Antigen 4 in the Pathogenesis of Multiple Sclerosis

Basile

Bramanti

Mazzon

2022

Genes

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Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder of the central nervous system that presents heterogeneous clinical manifestations and course. It has been shown that different immune checkpoints, including Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), can be involved in the pathogenesis of MS. CTLA-4 is a critical regulator of T-cell homeostasis and self-tolerance and represents a key inhibitor of autoimmunity. In this scopingreview, we resume the current preclinical and clinical studies investigating the role of CTLA-4 in MS with different approaches. While some of these studies assessed the expression levels of CTLA-4 on T cells by comparing MS patients with healthy controls, others focused on the evaluation of the effects of common MS therapies on CTLA-4 modulation or on the study of the CTLA-4 blockade or deficiency in experimental autoimmune encephalomyelitis models. Moreover, other studies in this field aimed to discover if the CTLA-4 gene might be involved in the predisposition to MS, whereas others evaluated the effects of treatment with CTLA4-Ig in MS. Although these results are of great interest, they are often conflicting. Therefore, further studies are needed to reveal the exact mechanisms underlying the action of a crucial immune checkpoint such as CTLA-4 in MS to identify novel immunotherapeutic strategies for MS patients.

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Influence of Genetic Polymorphisms on Clinical Outcomes of Glatiramer Acetate in Multiple Sclerosis Patients

Cited by 8 publications

References 104 publications

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

Efficacy of different intensity of aquatic exercise in enhancing remyelination and neuronal plasticity using cuprizone model in male Wistar rats

The Role of Cytotoxic T-Lymphocyte Antigen 4 in the Pathogenesis of Multiple Sclerosis

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